par Wang, Chengbin;Mao, Rui;Van De Casteele, Christine ;Pipeleers, Daniel;Ling, Zhidong
Référence American journal of physiology: endocrinology and metabolism, 292, 4, page (E1201-E1206)
Publication Publié, 2007-04
Article révisé par les pairs
Résumé : Pancreatic β-cells are the major extraneural site of glutamate decarboxylase expression (GAD). During culture of isolated β-cells, the GAD product β-aminobutyrate (GABA) is rapidly released in the medium, independently of insulin. It is considered as a possible mediator of γ-cell influences on α-cells, acinar cells, and/or infiltrating lymphocytes. In this perspective, we investigated the regulation of GABA release by rat β-cells during a 24-h culture period. Glucose was previously reported to inhibit GABA release by diverting cellular GABA to mitochondrial breakdown through activation of GABA transferase (GABA-T). In the present study, glucagon-like peptide-1 (GLP-1) was shown to stimulate GABA formation at the level of GAD, its effect being suppressed by the GAD inhibitor allylglycine and remaining unaltered by the GABA-T inhibitor γ-vinyl-GABA. The stimulatory action of GLP-1 is cAMP dependent, being reproduced by the adenylate cyclase activator forskolin and the cAMP analog N6-benzoyladenosine-3′, 5′-cAMP and inhibited by a PKA inhibitor. It is dependent on protein synthesis and associated with an increased expression of GAD67 but not GAD65. The GLP-1-induced stimulation of GAD activity in β-cells can elevate medium GABA levels in conditions of glucose-driven intracellular GABA breakdown and thus maintain GABA-mediated β-cell influences on neighboring cells. Copyright © 2007 the American Physiological Society.